The recent conclusions of Brasky et al must be examined closely as they are not only misleading but potentially dangerous. This statement may appear extreme, but omega-3 fatty acids have been repeatedly shown to protect us against cardiovascular disease (CVD), the leading cause of death in the Western World. Therefore, if men stop eating fish and taking fish oil pills for fear of prostate cancer, they may be putting themselves at risk for CVD, a disorder that kills seven times as many men as does prostate cancer. Such a decision would be not only unwise, but potentially damaging. To better understand this, let’s examine Brasky’s findings in the context of prior data as well as our understanding of the biology of DHA and EPA.

First, many earlier trials have demonstrated a correlation between high fish consumption and low rates of prostate cancer. Some examples are: Lancet, 2001 Terry et al showed a significant correlation between high fish consumption and a low incidence of prostate cancer. The Physician’s Health Study in 2008 revealed a correlation between high fish consumption and improved survival in men with prostate cancer. A 2003 Harvard study of 48,000 men showed a higher intake of fish to be associated with a lower risk of prostate cancer. There are many other examples, but this should suffice.

Second, let’s look at plasma levels of EPA and DHA in Brasky’s trial. The reported EPA+DHA level in the plasma phospholipids was 3.62% in the non-cancer control group and 3.74% in the high-grade cancer group. This difference between controls and the worst cases is extremely small, frankly with no clinical significance. It is simply within the normal laboratory variation.

Third, is association tantamount to cause? No. Even if there were a clear association between prostate cancer and high EPA and DHA levels, that would not prove causality. Other plausible explanations exist. In fact, this would more likely be a case of reverse causation. We know that two cancer-related phenomena will increase DHA and EPA levels. First, cancerous tissues can upregulate the genes for enzymes that cause long chain fatty acids to “grow” into EPA and DHA – the desaturases and elongases. Second, we know that genetic polymorphisms in the fatty acid desaturases are associated with an increased risk of cancer. So what may be occurring here (if anything is occurring at all) is that cancer-induced changes in desaturases, or cancer-producing genetic polymorphisms in these same enzymes are causing an increase in EPA and DHA. DHA and EPA are not causing the cancers.

Fourth, we are not told the source of omega-3s in this study group. Is it mostly from fish? Some fish have very high levels of PCBs, substances known to be carcinogenic. To conclude that people should stop their fish oil supplements when some supplements are actually far “cleaner” than fish, might therefore be very misguided.

Fifth, let’s examine another population with vastly different omega-3 levels to see whether Brasky’s assertions are relatable to real life. The Japanese consume eight times as much EPA and DHA as do Americans, yet their risk of prostate cancer is about one eighth of ours. If anything, one should conclude that omega-3s are protective here.

Sixth, we can’t ignore the biology of the fatty acids. A plethora of data has demonstrated the anti-inflammatory impact of the omega-3 fatty acids EPA and DHA. Data have also uniformly shown the pro-inflammatory effects of trans-fatty acids. When trial conclusions fly in the face of our understanding of human biology (in this case, trans fats not being harmful while omega-3s causing harm) we must consider them to be highly suspect.

Finally, let’s not forget that EPA and DHA are considered by experts to be “essential” fats. In other words, we must consume them in order to live. Before we discard these indispensable fatty acids, let’s await better clinical trials, and ones that are plausible in the context of prior literature and well-documented pathophysiology.

2 Comments

It can’t be a problem with fish oil since the Japanese (and others) who have very high consumption of fish are not dying en-mass of prostate cancer but it could be something associated with the supplement form of it. Most stuff is better in it’s natural form. I just wonder how much of the supplements are coming from China –

Or it may just be that men with otherwise unhealthy diet and lifestyle choices that might lead to prostate problems are just taking the EPA hoping to compensate and it isn’t working out.

This study stands out in what it didn’t say, not so much for what it did say.

Excellent response to a flawed study. It is hard to believe that such a flawed study can have an impact on health care science. My own physician told me two months ago that because of this study, he could no longer recommend fish oil supplements to his patients.

In the spirit of research, I suggest that maybe we can look at another high-risk procedure: CPR. I imagine that CPR is highly correlated with mortality, and a restrospective study would likely confirm this view. Can you imagine the headlines: CPR poses high risk for death